Friend MCF virus is a crucial intermediate in the induction of erythroleukemia after infection of newborn mice with Friend MuLV. Certain mouse strains endogenously express a novel glycoprotein, related to viral MCF gp70, which confers resistance by preventing the replication and spread of MCF viruses by a mechanism analogous to viral interference. Adult mice of susceptible strains are also resistant to F-MuLV-induced disease as the result of the failure to replicate MCF viruses due either to a lack of a suitable number of target cells or an effective immune response against the MCF viral envelope. Studies are presently being carried out to determine how the spleen focus-forming virus (SFFV) and Fr-MCF virus, which encode highly related envelope glycoproteins, interfere with erythropoiesis and why certain strains of mice are resistant to disease induced by these viruses. Erythroleukemia cell lines derived from the spleens of mice infected with either F-MuLV or the F-MuLV/SFFV complex were found to express high levels of a transformation-related phosphoprotein, p53. Studies are in progress to determine if an endogenous onc gene is being expressed at high levels in these cells.